Ekerfelt C, Andersson M, Olausson A, Bergström S, Hultman P
Division of Clinical Immunology, and Unit of Autoimmunity and Immune Regulation, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Clin Exp Immunol. 2007 Oct;150(1):189-97. doi: 10.1111/j.1365-2249.2007.03474.x. Epub 2007 Aug 2.
Lyme borreliosis is a complex infection, where some individuals develop so-called 'chronic borreliosis'. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl(2) (BbHg), controls exposed to HgCl(2) alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.
莱姆病螺旋体病是一种复杂的感染性疾病,部分个体可发展为所谓的“慢性莱姆病螺旋体病”。其发病机制尚不清楚,但免疫反应类型可能对疾病的治愈至关重要。有研究表明,强烈的1型辅助性T细胞(Th1)样反应对于根除伯氏疏螺旋体以及避免慢性病的发展至关重要。许多旨在改变莱姆关节炎患者Th1/Th2平衡的研究使用了细胞因子基因缺陷的小鼠,但结果并不明确,这可能是由于细胞因子具有高度冗余性。本研究旨在利用亚毒性剂量无机汞的Th2偏向效应,研究Th1/Th2平衡在小鼠伯氏疏螺旋体关节炎中的重要性。将98只C3H/HeN小鼠分为四组:伯氏疏螺旋体感染组(Bb)、感染伯氏疏螺旋体并暴露于HgCl₂的组(BbHg)、仅暴露于HgCl₂的对照组和正常对照组。在接种伯氏疏螺旋体后的第3天、16天、44天和65天处死小鼠。通过组织学评估关节炎严重程度,通过伯氏疏螺旋体培养确定螺旋体载量,通过酶联免疫吸附测定(ELISA)分析IgG2a和IgE水平,通过酶联免疫斑点法(ELISPOT)检测细胞因子分泌细胞。与Bb小鼠相比,BbHg小鼠的组织学关节炎症状较轻,但螺旋体清除延迟,同时IgE(Th2诱导)水平升高,IgG2a(Th1诱导)水平降低,这与Th2偏向一致。BbHg小鼠中Th1和Th2细胞因子分泌细胞的数量均减少,这可能是因为细胞因子分泌细胞的数量与细胞因子浓度并不相关。总之,本研究支持以下假设,即最佳根除伯氏疏螺旋体需要Th1样反应。